CN102553550A - Hybridization chirality stationary phase based on cellulose derivative and preparation method thereof - Google Patents
Hybridization chirality stationary phase based on cellulose derivative and preparation method thereof Download PDFInfo
- Publication number
- CN102553550A CN102553550A CN2012100114959A CN201210011495A CN102553550A CN 102553550 A CN102553550 A CN 102553550A CN 2012100114959 A CN2012100114959 A CN 2012100114959A CN 201210011495 A CN201210011495 A CN 201210011495A CN 102553550 A CN102553550 A CN 102553550A
- Authority
- CN
- China
- Prior art keywords
- cellulose derivative
- preparation
- phase
- chiral
- cellulose
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229920002678 cellulose Polymers 0.000 title claims abstract description 95
- 239000001913 cellulose Substances 0.000 title claims abstract description 95
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 230000005526 G1 to G0 transition Effects 0.000 title abstract description 19
- 238000009396 hybridization Methods 0.000 title abstract description 12
- 229910052710 silicon Inorganic materials 0.000 claims abstract description 29
- 239000010703 silicon Substances 0.000 claims abstract description 29
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 18
- 230000008021 deposition Effects 0.000 claims description 16
- 238000004132 cross linking Methods 0.000 claims description 15
- -1 propyl group isocyanates Chemical class 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 13
- 239000012948 isocyanate Substances 0.000 claims description 13
- 229910000077 silane Inorganic materials 0.000 claims description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims description 11
- 238000001914 filtration Methods 0.000 claims description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 238000001291 vacuum drying Methods 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 9
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims description 9
- 238000005406 washing Methods 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 239000000377 silicon dioxide Substances 0.000 claims description 8
- 238000001212 derivatisation Methods 0.000 claims description 7
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 6
- 239000004094 surface-active agent Substances 0.000 claims description 6
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 150000007984 tetrahydrofuranes Chemical group 0.000 claims description 5
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 4
- 239000013504 Triton X-100 Substances 0.000 claims description 4
- 229920004890 Triton X-100 Polymers 0.000 claims description 4
- 230000001376 precipitating effect Effects 0.000 claims description 4
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 claims description 3
- 238000000151 deposition Methods 0.000 claims description 2
- 239000013049 sediment Substances 0.000 claims description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 abstract description 27
- 239000002904 solvent Substances 0.000 abstract description 5
- 239000006087 Silane Coupling Agent Substances 0.000 abstract 1
- 238000003980 solgel method Methods 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
- 238000003756 stirring Methods 0.000 description 22
- 150000004676 glycans Chemical class 0.000 description 9
- 229920001282 polysaccharide Polymers 0.000 description 9
- 239000005017 polysaccharide Substances 0.000 description 9
- 239000011148 porous material Substances 0.000 description 9
- 150000003222 pyridines Chemical class 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 238000004090 dissolution Methods 0.000 description 7
- 238000000921 elemental analysis Methods 0.000 description 7
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 7
- 239000000178 monomer Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 238000002411 thermogravimetry Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QUNFCCQHRHTDDB-UHFFFAOYSA-N 1-chloro-3-isocyanato-5-methylbenzene Chemical compound CC1=CC(Cl)=CC(N=C=O)=C1 QUNFCCQHRHTDDB-UHFFFAOYSA-N 0.000 description 6
- MGYGFNQQGAQEON-UHFFFAOYSA-N 4-tolyl isocyanate Chemical class CC1=CC=C(N=C=O)C=C1 MGYGFNQQGAQEON-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000003513 alkali Substances 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- JKGITWJSGDFJKO-UHFFFAOYSA-N ethoxy(trihydroxy)silane Chemical class CCO[Si](O)(O)O JKGITWJSGDFJKO-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 229960001866 silicon dioxide Drugs 0.000 description 4
- ADAKRBAJFHTIEW-UHFFFAOYSA-N 1-chloro-4-isocyanatobenzene Chemical class ClC1=CC=C(N=C=O)C=C1 ADAKRBAJFHTIEW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 238000004237 preparative chromatography Methods 0.000 description 3
- XEFUJGURFLOFAN-UHFFFAOYSA-N 1,3-dichloro-5-isocyanatobenzene Chemical compound ClC1=CC(Cl)=CC(N=C=O)=C1 XEFUJGURFLOFAN-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000007445 Chromatographic isolation Methods 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000005557 chiral recognition Methods 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 238000011106 process-scale chromatography Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229940080264 sodium dodecylbenzenesulfonate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- QQQSFSZALRVCSZ-UHFFFAOYSA-N triethoxysilane Chemical compound CCO[SiH](OCC)OCC QQQSFSZALRVCSZ-UHFFFAOYSA-N 0.000 description 1
- YUYCVXFAYWRXLS-UHFFFAOYSA-N trimethoxysilane Chemical compound CO[SiH](OC)OC YUYCVXFAYWRXLS-UHFFFAOYSA-N 0.000 description 1
Images
Landscapes
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
The invention discloses a preparation method of a hybridization chirality stationary phase based on cellulose derivative, which cross-links non-replaced or replaced phenyl isocyanate cellulose derivative with silane coupling agents to prepare hybridization chirality silicon ball stationary phase in a sol-gel method and is simple in operation and easy to control. The prepared cellulose derivative of the hybridization chirality stationary phase is high in content, has good chirality resolution capability and mechanical strength, is good in solvent resistant property, has strong loading capability and is suitable for preparing chromatograph chairality stationary phase.
Description
Technical field
The present invention relates to the preparation field of chiral stationary phase, be specifically related to fixedly phase and preparation method thereof of a kind of hybrid chiral based on cellulose derivative.
Background technology
Progress and development along with medical science; The chromatogram of chiral drug splits and the analysis of optical purity becomes more and more important; Chiral stationary phase is a kind of chromatographic isolation material that enantiomer splits ability that has; Commercial at present chiral stationary phase has kind more than 100, and wherein the cellulose-derived chiral stationary phase has higher fractionation performance and chromatogram and uploads capacity, is widely used in the enantiomer analysis and separates preparation.
Existing cellulose derivative chiral stationary phase is with behind the cellulose hydroxyl derivatization, applies or is bonded to carrier surfaces such as silica gel and process.1986, Japanese Yoshio Okamoto group made a series of application type chiral stationary phases and successively develops application type cellulose derivative commodity post, like Chiralcel OD and OJ post etc.After this; For problem such as overcome in the coating-type chiral stationary phase that cellulose derivative is prone to run off and the solvent scope of application is narrow; Yoshio Okamoto etc. is bonded to aminopropyl silica gel through vulcabond with cellulose derivative first and makes the bonded chiral post, and Chiracel IB and IC be successful commercialization before and after 2004 years.China; Zou Hanfa etc. also disclose a kind of quick method for preparing the bonded polysaccharide chiral stationary phase in Chinese patent ZL200310105270.0; Step is: 1) in the reactor that fills organic solvent; Polysaccharide and polysaccharide derivatization reagent can react with the trimethoxy silane or the triethoxysilane of hydroxyl reaction functional group on the polysaccharide with containing, centrifugation, and it is subsequent use to collect solids; 2) contain trimethoxy or the triethoxy polysaccharide derivatives with above-mentioned preparation is coated on the exposed silica matrix surface that is usually used in chromatograph packing material; Be placed on then in the reactor, add a certain proportion of toluene and pyridine, after the reaction; Cooling; Use oxolane, methanol wash product more respectively, vacuum drying can make the bonded polysaccharide chiral stationary phase.The peaceful preparation method who then in Chinese patent ZL200710191730.4, discloses a kind of bonding-affine compound chiral stationary phase that waits of Liu Xiao, key step is: 1) with polysaccharide derivates I through being chemically bonded on the chiral stationary phase matrix, obtain fixedly phase of bonding type; 2) polysaccharide derivates II is coated to through affinity bonding type is fixing to be gone up mutually, obtains bonding-affinity composite type polysaccharide chiral stationary phase.
Yet; Because coating or bonding use the restriction of the pore volume of silica gel own; General only can bonding or apply the cellulose derivative of about 20wt%, make that the last carrying capacity of sample can't further improve in the preparative chromatography separation process, limited its application in process-scale chromatography.Simultaneously; The fixing mixture that can only adopt n-hexane and alcohol organic solvent mutually of application type cellulose is as flowing phase; Therefore possibly there are the problems such as enantiomer separation solubility in flowing phase is low of treating; Make the disposal ability of preparative chromatography decline to a great extent, even the economy of chromatographic separation process is had a greatly reduced quality; If in flowing phase, adding organic solvents such as acetone, oxolane, chloroform improves solubility property, thereby then can cause cellulose derivative to lose the chiral Recognition ability again.Though the bonding type cellulose is difficult for by dissolving of oxolane equal solvent or swelling; But because the bigger molecular dimension of cellulose derivative and the pore structure characteristic of silica-gel carrier itself; Make that the chirality function base density is lower than application type, carrying capacity and separative efficiency are not as good as application type on the sample.Therefore, develop and a kind ofly existingly upload capacity than rich shade spectrum, the wide chiral stationary phase of the solvent scope of application has vast market demand and application prospect simultaneously.
Summary of the invention
The invention provides the fixedly preparation method of phase of a kind of hybrid chiral based on cellulose derivative, prepared hybrid chiral is fixing to have good chiral resolution ability and mechanical strength mutually.
A kind of hybrid chiral based on cellulose derivative is the preparation method of phase fixedly, comprises step:
(1) cellulose is dissolved in N; In N-dimethylacetylamide/lithium chloride system; With the anhydrous pyridine is medium, adds the mixture of not replacement or substituted phenyl isocyanate derivatization reagent and three-(ethyoxyl silicon) propyl group isocyanates, carries out derivative reaction; Derivative reaction finishes back adding precipitating reagent makes the product deposition, and filtration and drying are not replaced or substituted phenyl isocyanate cellulose derivative;
(2) cellulose derivative in the step (1) is dissolved in the organic solvent; Add silane coupler again and carry out cross-linking reaction; Cross-linking products is added to burin-in process in the aqueous surfactant solution; The gained sediment obtains based on the hybrid chiral of cellulose derivative fixing mutually through filtration, washing and vacuum drying, i.e. organic inorganic hybridization silicon ball.
In order to reach better invention effect, preferably:
The unsubstituted or substituted phenyl isocyanate derivative reagent selection
The structural formula of described three-(ethyoxyl silicon) propyl group isocyanates is
Described three-(ethyoxyl silicon) propyl group isocyanates with do not replace or the mol ratio of substituted phenyl isocyanate derivatization reagent is 1: 9-99.
Described precipitating reagent is selected methyl alcohol or ethanol for use.
The mass ratio of described cellulose and three-(ethyoxyl silicon) propyl group isocyanates is 3-4: 1, be more conducive to the regulation and control of subsequent fixed phase porous character.
The ratio of the milliliter number of the gram number of described cellulose derivative and silane coupler is 0.02-0.1: 1, be more conducive to the regulation and control of subsequent fixed phase porous character.
Described silane coupler is selected a kind of in ethyl orthosilicate, two (triethoxy is silica-based) methane, two (triethoxy is silica-based) ethane for use, further preferred ethyl orthosilicate.
Described organic solvent is selected oxolane, pyridine, dimethyl sulfoxide (DMSO), chloroform or carrene for use.Described organic solvent preferably is heated to 30 ℃ of-80 ℃ of uses, is more conducive to the dissolving of cellulose derivative.
Described surfactant is selected ion-type or nonionic surface active agent for use; Specifically can select a kind of in lauryl sodium sulfate, softex kw, neopelex, OTAC, the Triton X-100 (Triton X-100) for use, further preferably sodium dodecyl sulfate and softex kw.Described aqueous surfactant solution preferably is heated to 40 ℃ of-100 ℃ of uses, and best vigorous stirring is 10 minutes-120 minutes during burin-in process, is more conducive to the formation of fixing mutually good microstructure.
The condition of described derivative reaction is 40 ℃-100 ℃ (further preferred 60 ℃-100 ℃) reactions 24 hours-72 hours.
The condition of described cross-linking reaction is 20 ℃-100 ℃ and reacted 1 hour-20 hours down.
Described cross-linking reaction is carried out under the condition of 2-11 in the pH value, and further being preferably in the pH value is to carry out under the condition of 2-7.
The used raw material of the present invention all can be selected the commercially available prod for use.
Fixedly the hybrid chiral based on cellulose derivative of preparation method's preparation of phase is fixing can be used for preparing chiral column mutually for described hybrid chiral based on cellulose derivative.
Compared with prior art, the present invention has following advantage:
The present invention adopts sol-gal process not replace or substituted phenyl isocyanate cellulose derivative is fixed mutually with the crosslinked preparation hybrid chiral of silane coupler silicon ball; Simple to operate; Be easy to control, prepared hybrid chiral is the cellulose derivative content height of phase fixedly, has good chiral resolution ability and mechanical strength; Solvent resistance is good and stronger upload capabilities is arranged, and is suitable as the chiral stationary phase that preparative chromatography is separated.
Description of drawings
Fig. 1 is the fractionation design sketch that Te Luogeer alkali
adopts the chiral column that embodiment 8 makes; Chromatographic condition is: 35 ℃ of column temperatures; Flowing phase be n-hexane/isopropyl alcohol (90: 10, v/v); Flow velocity 0.3mL/min; Detect wavelength 254nm;
Fig. 2 is the fractionation design sketch that Te Luogeer alkali
adopts the chiral column that embodiment 8 makes; Chromatographic condition is: 35 ℃ of column temperatures; Flowing phase be n-hexane/chloroform/isopropyl alcohol (90: 10: 1, v/v/v); Flow velocity 0.3mL/min; Detect wavelength 254nm;
Among the figure, the peak of the left-handed Te Luogeer alkali of (-) expression, the peak of (+) expression dextrorotation Te Luogeer alkali, ordinate is a response, abscissa is the time: minute.
The specific embodiment
Embodiment 1:
1) phenyl isocyanate cellulose derivative chirality silane monomer is synthetic
With 0.2 gram cellulose and an amount of N; The N-dimethylacetylamide places there-necked flask with an amount of lithium chloride, and stirring and refluxing 1 hour is treated to add 2 milliliters of anhydrous pyridines behind the cellulose dissolution; The mixture that adds 0.62 gram (0.005mol) phenyl isocyanate and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanates again; Stir under 80 ℃ and carried out derivative reaction 24 hours, make the product deposition with 200 ml methanol then, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
After cellulose derivative is dissolved in 70 ℃ of oxolanes with 0.1 gram; Add 2 milliliters of ethyl orthosilicates and 1 ml water successively; Add acid for adjusting pH to 2,60 ℃ of following cross-linking reactions 2 hours, it was in 5% the lauryl sodium sulfate aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 60 ℃ of mass percentage concentration; And in 60 ℃ of vigorous stirring 120 minutes; The deposition that obtains is used sand core funnel to filter and used concentration expressed in percentage by volume successively is 50% ethanol water, n-hexane washing, and vacuum drying 8 hours promptly gets fixedly phase of phenyl isocyanate cellulose-derived chiral hybrid.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 80%; Fixedly the phase specific area is 190m
2/ g, average pore size is 13nm.
Embodiment 2:
1) 4-chlorphenyl isocyanates cellulose derivative chirality silane monomer is synthetic
With 0.2 gram cellulose and an amount of N, the N-dimethylacetylamide places there-necked flask with an amount of lithium chloride, and 70 ℃ of following stirring and refluxing 1 hour are treated to add 2 milliliters of anhydrous pyridines behind the cellulose dissolution.Add 1.23 gram 4-chlorphenyl isocyanates (0.008mol) and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanate mixture again; Stir under 80 ℃ and carried out derivative reaction 24 hours; Make the product deposition with 200 milliliters of ethanol then, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
After cellulose derivative is dissolved in 70 ℃ of oxolanes with 0.11 gram; Add 4 milliliters of ethyl orthosilicates and 1 ml water successively; Regulate pH to 3,60 ℃ of following cross-linking reactions 2 hours, it was in 5% the lauryl sodium sulfate aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 60 ℃ of mass percentage concentration; And in 60 ℃ of vigorous stirring 50 minutes; The deposition that obtains is used sand core funnel to filter and used concentration expressed in percentage by volume successively is 50% ethanol water, n-hexane washing, and vacuum drying 8 hours promptly gets fixedly phase of 4-chlorphenyl isocyanates cellulose-derived chiral hybrid silicon ball.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 65%; Fixedly the phase specific area is 197m
2/ g, average pore size is 14.6nm.
Embodiment 3:
1) p-methylphenyl isocyanates cellulose derivative chirality silane monomer is synthetic
With 0.2 gram cellulose and an amount of N, the N-dimethylacetylamide places there-necked flask with an amount of lithium chloride, and 70 ℃ of following stirring and refluxing 1 hour are treated to add 2 milliliters of anhydrous pyridines behind the cellulose dissolution.The mixture that adds 0.85 gram p-methylphenyl isocyanates (0.0064mol) and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanates again; Stir under 80 ℃ and carried out derivative reaction 24 hours; Make the product deposition with 200 ml methanol then, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
After cellulose derivative is dissolved in 70 ℃ of oxolanes with 0.09 gram; Add 3 milliliters of ethyl orthosilicates and 1 ml water successively; Regulate pH to 7,60 ℃ of following cross-linking reactions 2 hours, it was in 5% the lauryl sodium sulfate aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 60 ℃ of mass percentage concentration; And in 60 ℃ of vigorous stirring 10 minutes; The deposition that obtains is used sand core funnel to filter and used concentration expressed in percentage by volume successively is 50% ethanol water, n-hexane washing, and vacuum drying 8 hours promptly gets fixedly phase of p-methylphenyl isocyanates cellulose-derived chiral hybrid silicon ball.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 72%:; Fixedly the phase specific area is 200m
2/ g, average pore size is 15nm.
Embodiment 4:
1) 3,5-dichlorophenyl isocyanate cellulose derivative chirality silane monomer synthetic
With 0.2 gram cellulose and an amount of N; The N-dimethylacetylamide places there-necked flask with an amount of lithium chloride; 70 ℃ of following stirring and refluxing 1 hour are treated to add 2 milliliters of anhydrous pyridines behind the cellulose dissolution, add 1.24 grams 3 again; The mixture of 5-dichlorophenyl isocyanate (0.0066mol) and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanates; Stir under 80 ℃ and carried out derivative reaction 24 hours, make the product deposition with 200 ml methanol then, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
After cellulose derivative is dissolved in 70 ℃ of oxolanes with 0.13 gram; Add 2 milliliters of ethyl orthosilicates and 1 ml water successively, add acid for adjusting pH to 3,60 ℃ of following cross-linking reactions 2 hours; It is in 5% the softex kw aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 60 ℃ of mass percentage concentration; And in 60 ℃ of vigorous stirring 80 minutes, the deposition that obtains is used sand core funnel to filter and used concentration expressed in percentage by volume successively was 50% ethanol water, n-hexane washing, vacuum drying 8 hours; Promptly get 3,5-dichlorophenyl isocyanate cellulose-derived chiral hybrid is phase fixedly.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 83%; Fixedly the phase specific area is 220m
2/ g, average pore size is 12nm.
Embodiment 5:
1) 3-methyl-5-chloro phenyl isocyanate cellulose derivative chirality silane monomer is synthetic
With 0.2 gram cellulose and an amount of N, the N-dimethylacetylamide places there-necked flask with an amount of lithium chloride, and 70 ℃ of following stirring and refluxing 1 hour are treated to add 2 milliliters of anhydrous pyridines behind the cellulose dissolution.Add 3.32 gram 3-methyl-5-chloro phenyl isocyanate (0.0198mol) and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanate mixture again; Stir under 100 ℃ and carried out derivative reaction 72 hours; Make the product deposition with 200 milliliters of ethanol then, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
After cellulose derivative is dissolved in 80 ℃ of pyridines with 0.1 gram; Add 4 milliliters of two (triethoxy is silica-based) methane and 1 ml water successively; Regulate pH to 3,100 ℃ of following cross-linking reactions 1 hour, it was in 10% the sodium dodecyl benzene sulfonate aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 40 ℃ of mass percentage concentration; And in 40 ℃ of vigorous stirring 120 minutes; The deposition that obtains is used sand core funnel to filter and used concentration expressed in percentage by volume successively is 50% ethanol water, n-hexane washing, and vacuum drying 8 hours promptly gets fixedly phase of 3-methyl-5-chloro phenyl isocyanate cellulose-derived chiral hybrid silicon ball.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 64%; Fixedly the phase specific area is 180m
2/ g, average pore size is 15nm.
Embodiment 6:
1) 3-methyl-5-chloro phenyl isocyanate cellulose derivative chirality silane monomer is synthetic
With 0.2 gram cellulose and an amount of N, the N-dimethylacetylamide places there-necked flask with an amount of lithium chloride, and 70 ℃ of following stirring and refluxing 1 hour are treated to add 2 milliliters of anhydrous pyridines behind the cellulose dissolution.Add 0.3 gram 3-methyl-5-chloro phenyl isocyanate (0.0018mol) and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanate mixture again; Stir under 60 ℃ and carried out derivative reaction 48 hours; Make the product deposition with 200 milliliters of ethanol then, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
After cellulose derivative is dissolved in 30 ℃ of chloroforms with 0.1 gram; Add 4 milliliters of two (triethoxy is silica-based) ethane and 1 ml water successively; Regulate pH to 2,20 ℃ of following cross-linking reactions 20 hours, it was in 3% the OTAC aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 100 ℃ of mass percentage concentration; And in 100 ℃ of vigorous stirring 10 minutes; The deposition that obtains is used sand core funnel to filter and used concentration expressed in percentage by volume successively is 50% ethanol water, n-hexane washing, and vacuum drying 8 hours promptly gets fixedly phase of 3-methyl-5-chloro phenyl isocyanate cellulose-derived chiral hybrid silicon ball.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 65%; Fixedly the phase specific area is 186m
2/ g, average pore size is 15nm.
Embodiment 7:
1) p-methylphenyl isocyanates cellulose derivative chirality silane monomer is synthetic
With 0.2 gram cellulose and an amount of N, the N-dimethylacetylamide places there-necked flask with an amount of lithium chloride, and 70 ℃ of following stirring and refluxing 1 hour are treated to add 2 milliliters of anhydrous pyridines behind the cellulose dissolution.Add 1.33 gram p-methylphenyl isocyanates (0.01mol) and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanate mixture again; Stir under 40 ℃ and carried out derivative reaction 55 hours; Make the product deposition with 200 milliliters of ethanol then, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
After cellulose derivative is dissolved in 50 ℃ of dimethyl sulfoxide (DMSO)s with 0.1 gram; Add 4 milliliters of two (triethoxy is silica-based) ethane and 1 ml water successively; Regulate pH to 11,50 ℃ of following cross-linking reactions 10 hours, it was in 5% the Triton X-100 aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 80 ℃ of mass percentage concentration; And in 80 ℃ of vigorous stirring 30 minutes; The deposition that obtains is used sand core funnel to filter and used concentration expressed in percentage by volume successively is 50% ethanol water, n-hexane washing, and vacuum drying 8 hours promptly gets fixedly phase of p-methylphenyl isocyanates cellulose-derived chiral hybrid silicon ball.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 62%; Fixedly the phase specific area is 182m
2/ g, average pore size is 15.5nm.
Embodiment 8:
With 3 of embodiment 4 preparations, the fixing wet method dress post that uses mutually of 5-dichlorophenyl isocyanate cellulose-derived chiral hybrid silicon ball prepares the chiral column of specification as 4.6mm * 150mm.The chiral column that makes is used to split Te Luogeer alkali
chromatographic condition: 35 ℃ of column temperatures; Flowing phase be n-hexane/isopropyl alcohol (90: 10, v/v); Flow velocity 0.3mL/min; Detect wavelength 254nm; Split effect and see Fig. 1 and Fig. 2.
Claims (10)
1. one kind based on the fixing preparation method of phase of the hybrid chiral of cellulose derivative, comprises step:
(1) cellulose is dissolved in N; In N-dimethylacetylamide/lithium chloride system; With the anhydrous pyridine is medium, adds the mixture of not replacement or substituted phenyl isocyanate derivatization reagent and three-(ethyoxyl silicon) propyl group isocyanates, carries out derivative reaction; Derivative reaction finishes back adding precipitating reagent makes the product deposition, and filtration and drying obtain cellulose derivative;
(2) cellulose derivative in the step (1) is dissolved in the organic solvent; Add silane coupler again and carry out cross-linking reaction; Cross-linking products is added to burin-in process in the aqueous surfactant solution, and the gained sediment obtains based on the hybrid chiral of cellulose derivative fixing mutually through filtration, washing and vacuum drying.
2. the hybrid chiral based on cellulose derivative according to claim 1 is the preparation method of phase fixedly, it is characterized in that, described replace or substituted phenyl isocyanate derivatization reagent does
3. the hybrid chiral based on cellulose derivative according to claim 1 is the preparation method of phase fixedly; It is characterized in that, described three-(ethyoxyl silicon) propyl group isocyanates with do not replace or the mol ratio of substituted phenyl isocyanate derivatization reagent is 1: 9-99.
4. the hybrid chiral based on cellulose derivative according to claim 1 is the preparation method of phase fixedly, it is characterized in that described precipitating reagent is methyl alcohol or ethanol.
5. the hybrid chiral based on cellulose derivative according to claim 1 is the preparation method of phase fixedly, it is characterized in that, described silane coupler is a kind of in ethyl orthosilicate, two (triethoxy is silica-based) methane, two (triethoxy is silica-based) ethane.
6. the hybrid chiral based on cellulose derivative according to claim 1 is the preparation method of phase fixedly; It is characterized in that described surfactant is a kind of in lauryl sodium sulfate, softex kw, neopelex, OTAC, the Triton X-100.
7. the hybrid chiral based on cellulose derivative according to claim 1 is the preparation method of phase fixedly, it is characterized in that described organic solvent is oxolane, pyridine, dimethyl sulfoxide (DMSO), chloroform or carrene.
8. the hybrid chiral based on cellulose derivative according to claim 1 is the preparation method of phase fixedly, it is characterized in that, the condition of described derivative reaction is 40 ℃-100 ℃ reactions 24 hours-72 hours;
Perhaps, the condition of described cross-linking reaction is to react 1 hour-20 hours under 20 ℃-100 ℃;
Perhaps, described cross-linking reaction is carried out under the condition of 2-11 in the pH value.
According to each described hybrid chiral based on cellulose derivative of claim 1-8 fixedly phase preparation method's preparation based on the fixing phase of the hybrid chiral of cellulose derivative.
10. the fixing application in the preparation chiral chromatographic column of the hybrid chiral based on cellulose derivative according to claim 9.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210011495 CN102553550B (en) | 2012-01-13 | 2012-01-13 | Hybridization chirality stationary phase based on cellulose derivative and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210011495 CN102553550B (en) | 2012-01-13 | 2012-01-13 | Hybridization chirality stationary phase based on cellulose derivative and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102553550A true CN102553550A (en) | 2012-07-11 |
| CN102553550B CN102553550B (en) | 2013-11-06 |
Family
ID=46400950
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201210011495 Expired - Fee Related CN102553550B (en) | 2012-01-13 | 2012-01-13 | Hybridization chirality stationary phase based on cellulose derivative and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102553550B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104741102A (en) * | 2013-12-30 | 2015-07-01 | 中国科学院兰州化学物理研究所 | A preparing method of a surface organic-inorganic hybrid core-shell type polysaccharide chiral stationary phase |
| CN105080518A (en) * | 2014-05-13 | 2015-11-25 | 中科院大连化学物理研究所淮安化工新材料研究中心 | Chemically-bonded cellulose-type chiral stationary phase and preparation method thereof |
| CN105289559A (en) * | 2014-12-08 | 2016-02-03 | 浙江月旭材料科技有限公司 | Preparation method of bonding type stationary phase chiral chromatographic column |
| CN109012636A (en) * | 2018-09-04 | 2018-12-18 | 济宁医学院 | A kind of preparation method of width pH range cyclodextrin hybrid silicon microballoon chiral stationary phase |
| CN113908813A (en) * | 2021-10-22 | 2022-01-11 | 浙江大学衢州研究院 | Cellulose derivative-silicon-based hybrid microsphere and preparation method thereof |
-
2012
- 2012-01-13 CN CN 201210011495 patent/CN102553550B/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| TOMOYUKI IKAI ET AL.: "Immobilization of polysaccharide derivatives onto silica gel Facile synthesis of chiral packing materials by means of intermolecular polycondensation of triethoxysilyl groups", 《JOURNAL OF CHROMATOGRAPHY A》 * |
| TOMOYUKI IKAI ET AL.: "Organic-Inorganic Hybrid Materials for Efficient Enantioseparation Using Cellulose 3,5-Dimethylphenylcarbamate and Tetraethyl Orthosilicate", 《 CHEM. ASIAN J.》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104741102A (en) * | 2013-12-30 | 2015-07-01 | 中国科学院兰州化学物理研究所 | A preparing method of a surface organic-inorganic hybrid core-shell type polysaccharide chiral stationary phase |
| CN104741102B (en) * | 2013-12-30 | 2017-02-22 | 中国科学院兰州化学物理研究所 | A preparing method of a surface organic-inorganic hybrid core-shell type polysaccharide chiral stationary phase |
| CN105080518A (en) * | 2014-05-13 | 2015-11-25 | 中科院大连化学物理研究所淮安化工新材料研究中心 | Chemically-bonded cellulose-type chiral stationary phase and preparation method thereof |
| CN105289559A (en) * | 2014-12-08 | 2016-02-03 | 浙江月旭材料科技有限公司 | Preparation method of bonding type stationary phase chiral chromatographic column |
| CN105289559B (en) * | 2014-12-08 | 2018-04-20 | 浙江月旭材料科技有限公司 | A kind of preparation method of bonding type stationary phase chiral chromatographic column |
| CN109012636A (en) * | 2018-09-04 | 2018-12-18 | 济宁医学院 | A kind of preparation method of width pH range cyclodextrin hybrid silicon microballoon chiral stationary phase |
| CN113908813A (en) * | 2021-10-22 | 2022-01-11 | 浙江大学衢州研究院 | Cellulose derivative-silicon-based hybrid microsphere and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102553550B (en) | 2013-11-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102553550B (en) | Hybridization chirality stationary phase based on cellulose derivative and preparation method thereof | |
| CN100579650C (en) | Preparation of bonding-affinity composite type polysaccharides chiral stationary phase | |
| CN101992076B (en) | Chiral binaphthyl chromatogram immobile phase, and preparation method and application thereof | |
| CN103706341B (en) | Ionic liquid bonding polysiloxane stationary phase and preparation method thereof | |
| CN104262496A (en) | Chiral stationary phase of bonding amylose derivative and preparing method thereof | |
| Shen et al. | Synthesis of cellulose carbamates bearing regioselective substituents at 2, 3-and 6-positions for efficient chromatographic enantioseparation | |
| CN103406113A (en) | Preparation method of immobilized beta-cyclodextrin derivative type chiral stationary phase | |
| CN105254499B (en) | A kind of phenolic hydroxy group eleostearate alkylated compound and its preparation method and application | |
| Dai et al. | Chiral recognition ability of amylose derivatives bearing regioselectively different carbamate pendants at 2, 3-and 6-positions | |
| CN101417227B (en) | Silica gel bonded double-chirality active center chromatogram filler and use thereof | |
| CN103551118B (en) | Column [5] aromatic bonding silica gel stationary phase as well as preparation method and application thereof | |
| Shen et al. | Synthesis and chiral recognition of amylose derivatives bearing regioselective phenylcarbamate substituents at 2, 6-and 3-positions for high-performance liquid chromatography | |
| CN101717513B (en) | Hybrid ordered mesoporous silica gel chromatograph stationary-phase stuffing and preparation method thereof | |
| CN105080518A (en) | Chemically-bonded cellulose-type chiral stationary phase and preparation method thereof | |
| Shen et al. | Immobilization and chromatographic evaluation of novel regioselectively substituted amylose‐based chiral packing materials for HPLC | |
| CN105772080A (en) | Kieselguhr load palladium catalyst, preparing method and application thereof | |
| CN102516400B (en) | Preparation method for mesoporous-silica-based cellulose bonding chiral stationary phase | |
| CN107096509A (en) | The sephadex and preparation method of a kind of succinic acid of amido containing α function base | |
| CN105688858B (en) | A kind of Amylose Chiral Stationary Phase and preparation method thereof | |
| CN103846103A (en) | Silica gel loaded type catalyst and application of catalyst in Baeyer-Villiger reaction | |
| CN103736469B (en) | A kind of ionic liquid bonding polysiloxane stationary phase and preparation method thereof | |
| CN105017437A (en) | Regioselective synthesis and application methods for amylose derivatives with different carbamate side groups | |
| CN103923090B (en) | The preparation method of Isosorbide-5-Nitrae-porphyrin-dihydropyridine-graphene oxide compound | |
| CN103965484B (en) | Preparation method and application of omega-diamine derivatization beta-cyclodextrin bonded SBA-15 chiral stationary phase | |
| CN102489276A (en) | Benzyl nitrogen bridged calix[2]arene[2]triazine bonded silica stationary phase, its preparation method and its purpose |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20131106 |